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Geron Corporation (GERN) is a late-stage biopharmaceutical company focused on the treatment of blood cancers by targeting and inhibiting the enzyme telomerase. The company’s first-in-class telomerase inhibitor product candidate, Imetelstat, is currently undergoing two phase 3 clinical trials for blood cancer disease indications.
Telomeres are DNA sequences that act as protective caps at the end of chromosomes to maintain stability of the cell's genetic material. Growth and maintenance of tissues within the human body occurs through cell division, and the number of possible cell divisions is regulated by telomere length because, under normal circumstances, the telomeres shorten with each cell division. However, there are some cases when telomeres need to be prevented from shortening, like during embryonic development, so that cells can divide rapidly and promote growth during that stage. In these instances, telomerase, which is an actively occurring enzyme that prevents telomeres from shortening during cell division, activates in the body to maintain the telomeres length.
Although telomerase plays a vital role in our bodies, it can also be a detriment when cancer is present. Telomerase activity has been found in approximately 90% of biopsies taken from a broad range of cancers. Although the presence of telomerase doesn’t appear to cause cells to become cancerous, it does enable tumor cells an unchecked ability to multiply and spread because they are able to avoid the cell death that would normally occur.
To combat hematologic malignancies, or blood cancers, Geron has discovered and developed imetelstat. Imetelstat is an oligonucleotide, which are small pieces of nucleic acid used to detect and bind to targeted segments of RNA or DNA. Because telomerase consists of an RNA template, imetelstat is able to directly inhibit telomerase activity by binding with the RNA template of telomerase.
Myelodysplastic Syndromes (MDS) are a group of cancers that occur when the blood-forming cells in the bone marrow become abnormal and cause inefficient production and low numbers in multiple types of blood cells. These low blood cell counts can lead to severe anemia, life-threatening infections, and bleeding. MDS is one of the most common blood cancers, with around 20,000 cases reported in just the US each year. The majority 70% of patients fall into the lower risk group for the disease, for which chronic anemia is the major clinical issue of patients.
Current drug therapies for the broad treatment of lower risk MDS either aren’t effective or lose their effectiveness over time, resulting in patients becoming dependent on red blood cell transfusions. Serial red blood cell transfusions can become dangerous for patients because they cause the buildup of iron in the body, which is associated with poorer survival rates and a higher risk of developing acute myelogenous leukemia (AML). IMerge is a phase 3 clinical trial evaluating imetelstat for MDS patients who are dependent on transfusions that is being conducted in over 100 medical centers across the globe. Results have been very promising, with 29% of patients being able to avoid a blood transfusion for at least a year, 75% seeing a rise in hemoglobin during the transfusion-free period, and reductions in mutations and abnormalities.
Geron expects top-line results for IMerge to be available in January 2023, after which they plan to submit a new drug application in the United States by mid-2023 and a marketing authorization application in Europe in the second half of 2023. The company’s goal is a commercial launch of imetelstat for lower-risk MDS in 2024.
Myelofibrosis (MF) is a chronic blood cancer that affects up to 18,500 people in the United States and is characterized by the rapid growth of cancer cells in the bone marrow, causing scar tissue or fibrosis to form. This impairs normal blood production, which causes many MF patients to suffer from chronic symptoms like night sweats, fatigue, severe itching, bone pain, fever, and abdominal pain. Up to 20% of MF patients eventually develop AML. Currently approved drug therapies for MF, one of which is JAK inhibitor treatment, are not effective for all patients, leaving many without a long-term solution.
IMpactMF is a phase 3 clinical trial using imetelstat to treat MF patients where JAK inhibitor treatment has been shown ineffective. Although interim analysis for IMpactMF is not expected until 2024, phase 2 trials of imetelstat showed very promising results, with a 65% - 67% decrease in death risk with imetelstat treatment compared with the next best alternative treatment available.
Although the potential for commercialization and product revenue appears close at hand with the progress of current phase 3 trials, Geron has yet to generate any revenue from commercialized products and has accumulated an operating deficit of well over $1 billion. The company previously generated revenue from licenses and collaboration agreements, but currently has no revenue generating arrangements in place or plans to enter into collaborations or partnerships involving imetelstat.
Geron expects to fund future operations through equity offerings, debt financings, collaborations, strategic partnerships, and other marketing and distribution arrangements. The company has an active equity securities issuance agreement with B. Riley Securities, for which it can issue and sell up to $100 million in common stock. If Geron is forced to utilize this agreement to a large extent for funding needs, it could result in stock dilution for current shareholders.
Geron’s imetelstat product candidate has major potential for improving treatment of blood cancers and could become a primary treatment option. If approved, imetelstat stands to generate considerable revenues for Geron, with the company planning to commercialize the drug product itself in the US and obtain commercialization partners in territories beyond.
Treatment of MDS and MF with imetelstat are also patent protected until 2033 in both the US and EU, leaving Geron with approximately a decade of potentially low direct competition in two highly lucrative markets. After over 30 years of operations, sometime within the 5-10 years, Geron Corporation could finally commercialize its first product for sale and provides blood cancer patients an enhanced treatment option to prolong lifespan and improve quality of life.